Disorders of intracranial pressure, including traumatic brain injury and hydrocephalus, can cause significant morbidity and mortality. There is increasing evidence that many of our "standard" theories explaining the pathophysiology of these disorders should be reconsidered. In this proposal, a novel theory describing the pathophysiology of elevated intracranial pressure and hydrocephalus is studied using a combination of bioengineering modeling methods and laboratory experimental investigations. The theory, which we termed the hemodynamic theory, is based on an interrelationship between intracranial compliance, cerebral blood flow impedance, and intracranial pressure. Our preliminary studies using a small animal model have demonstrated a strong correlation between compliance and disturbances in blood flow. The overall objective of this project is to construct and validate a transmission-line circuit that models intracranial pressure changes in relationship to altered hemodynamics. In order to enhance the accuracy of the model, the individual circuit parameters will be estimated from in vitro experiments. In addition, an in vivo model of acute hydrocephalus will be used to test the theoretical basis supporting the circuit model. Finally, the computer simulations of the new circuit model will be compared to the actual physiological data derived from the animal experiments. The long-term goal of this project is to establish a comprehensive, unifying theory of intracranial pressure pathophysiology that accurately represents and predicts the various clinical disorders affected by altered intracranial pressure. The use of bioengineering modeling techniques provides a powerful method to test hypotheses by simulating complex physiologic phenomenon. An improved understanding of these disorders will offer new and better treatment modalities for millions of affected patients.